Project description
Reprogramming cancer cells into immune cells with RNA therapy
Many solid tumours remain refractory to immunotherapy, mainly due to their immunosuppressive environment associated with hypoxia, low pH and nutrient availability. The ERC-funded DART project proposes an alternative immunotherapeutic approach: converting tumour cells to dendritic cells to boost tumour antigen presentation. The study builds on previously developed technology where the expression of specific transcription factors by tumour cells can induce them to transdifferentiate into dendritic cells. DART researchers aim to develop RNA vectors for in vivo reprogramming of tumour cells, enhancing anti-tumour immunity. The long-term plan is generation of a scalable, off-the-shelf immunotherapy solution to boost current treatments.
Objective
Immunotherapy has transformed cancer treatment, but targeting effectively refractory solid tumors remains a challenge due to poor T cell activation. Downregulation of antigen presentation pathways and lack of professional antigen presenting cells in the tumor microenvironment contribute to immune evasion. My group has demonstrated direct reprogramming of fibroblasts or tumor cells into type 1 conventional dendritic cells (cDC1) cells by overexpression of the transcription factors PU.1 IRF8, and BATF3, moving towards clinical application via a viral gene therapy. Despite its potential for first-in-class therapy, viral approaches still face limitations including inefficient targeting of solid tumors in vivo and challenging scalability.
The DART project builds on the ERC-funded project TrojanDC and aims to develop in vivo reprogramming of tumor cells into cDC1-like cells using RNA vectors. I will firstly evaluate the capacity of modified linear, self-replicating, and circular RNA encoding the factors to reprogram fibroblasts in vitro and assess their antigen presentation and cytokine secretion function. Secondly, I will evaluate RNA-mediated reprogramming of cancer cells and assess anti-tumor immunity in vivo as monotherapy and in combination with immune checkpoint blockade. The goal is to optimize RNA vector designs for the most effective in vivo reprogramming considering differences in delivery efficiency, expression kinetics and immunogenicity. Collaborations with clinicians and industry partners like Asgard Therapeutics are integral, ensuring commercialization through novel intellectual property, broad dissemination, and product development.
DART will enable RNA-mediated induction of antigen-presenting phenotypes in cancer cells, leading to potent and specific immunity towards tumor-specific antigens. DART will result in an off-the-shelf, safe, and scalable immunotherapy solution that also has the potential to enhance current immunotherapy approaches.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine immunology immunotherapy
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-POC
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
22100 Lund
Sweden
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.